Regulation of eosinophil trafficking by SWAP-70 and its role in allergic airway inflammation.
Regulation of eosinophil trafficking by SWAP-70 and its role in allergic airway inflammation.
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DOI：
10.4049/jimmunol.1102253
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发表时间：
2012-02-01
期刊：
影响因子：
--
通讯作者：
Sriramarao P
中科院分区：
文献类型：
--
作者：
Bahaie NS;Hosseinkhani MR;Ge XN;Kang BN;Ha SG;Blumenthal MS;Jessberger R;Rao SP;Sriramarao P
嗜酸性粒细胞是招募到过敏性气道的主要炎性细胞。在这里，我们表明，人类和小鼠嗜酸性粒细胞表达SWAP-70，细胞内RAC结合信号蛋白，并检查其在介导嗜酸性粒细胞贩运和肺部招募在小鼠过敏性气道炎症模型的作用。与WT嗜酸性粒细胞相比，SWAP-70缺陷型（Swap-70−/−）嗜酸性粒细胞在血流条件下通过活体显微镜观察发现炎症毛细血管后小静脉内的粘附相互作用发生改变，表现出缓慢滚动增强，但粘附牢固性降低。在静态粘附试验中，Swap-70−/−嗜酸性粒细胞与VCAM-1和ICAM-1的粘附较差，并表现出无效的前缘和尾足形成。粘附的Swap-70−/−嗜酸性粒细胞未能将RAC 1转移到前缘，并显示α4和Mac-1的异常细胞表面定位/分布。趋化因子诱导的Swap-70−/−嗜酸性粒细胞迁移显著降低，与细胞内钙水平降低、肌动蛋白聚合/解聚缺陷和细胞骨架重排改变相关。在体内，与WT小鼠相比，变应原激发Swap-70−/−小鼠肺中嗜酸性粒细胞的募集显著减少，沿着气道炎症显著减弱，表现为IL-5、IL-13和TNFα水平降低、粘液分泌减少和气道功能改善。这些发现表明，SWAP-70对嗜酸性粒细胞运输和迁移的调节对于过敏原暴露后嗜酸性粒细胞炎症的发展是重要的。
Eosinophils are the predominant inflammatory cells recruited to allergic airways. Here we demonstrate that human and murine eosinophils express SWAP-70, an intracellular RAC-binding signaling protein, and examine its role in mediating eosinophil trafficking and pulmonary recruitment in a murine model of allergic airway inflammation. Compared to WT eosinophils, SWAP-70 deficient (Swap-70−/−) eosinophils revealed altered adhesive interactions within inflamed post capillary venules under conditions of blood flow by intravital microscopy exhibiting enhanced slow rolling but decreased firm adhesion. In static adhesion assays, Swap-70−/− eosinophils adhered poorly to VCAM-1 and ICAM-1 and exhibited inefficient leading edge and uropod formation. Adherent Swap-70−/− eosinophils failed to translocate RAC1 to leading edges and displayed aberrant cell surface localization/distribution of α4 and Mac-1. Chemokine-induced migration of Swap-70−/− eosinophils was significantly decreased correlating with reduced intracellular calcium levels, defective actin polymerization/depolymerization and altered cytoskeletal rearrangement. In vivo, compared to WT mice, recruitment of eosinophils to the lungs of allergen-challenged Swap-70−/− mice was significantly reduced along with considerable attenuation of airway inflammation indicated by diminished IL-5, IL-13 and TNFα levels, reduced mucus secretion and improved airway function. These findings suggest that regulation of eosinophil trafficking and migration by SWAP-70 is important for the development of eosinophilic inflammation after allergen exposure.
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影响因子：
14.2
作者：
Boyce, Joshua A.;Broide, David;Matsumoto, Kenji;Bochner, Bruce S.
通讯作者：
Bochner, Bruce S.
影响因子：
6.4
作者：
Amaral, Maria M.;Alvarez, Carolina;Vermeulen, Monica
通讯作者：
Vermeulen, Monica
影响因子：
15.9
作者：
COSTA, JJ;MATOSSIAN, K;GALLI, SJ
通讯作者：
GALLI, SJ
影响因子：
4.6
作者：
Grailer JJ;Kodera M;Steeber DA
通讯作者：
Steeber DA
DOI：
10.4049/jimmunol.1000039
发表时间：
2010-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ge XN;Bahaie NS;Kang BN;Hosseinkhani MR;Ha SG;Frenzel EM;Liu FT;Rao SP;Sriramarao P
通讯作者：
Sriramarao P